Version May 2024
Hepatitis B virus (HBV) reactivation can occur in patients receiving CD20-directed cytolytic antibodies, including ofatumumab, in some cases resulting in fulminant hepatitis, hepatic failure, and death.
Progressive multifocal leukoencephalopathy (PML) resulting in death can occur in patients receiving CD20-directed cytolytic antibodies, including ofatumumab.
Note: IV: Premedicate with acetaminophen, an antihistamine, and a corticosteroid 30 to 120 minutes prior to treatment (see "Premedication" below). Consider tumor lysis prophylaxis with antihyperuricemic therapy and aggressive hydration beginning 12 to 24 hours prior to ofatumumab infusion; correct electrolyte abnormalities.
Chronic lymphocytic leukemia (CLL), previously untreated: Arzerra: IV: Cycle 1 (cycle is 28 days): 300 mg on day 1, followed by 1,000 mg on day 8; Subsequent cycles: 1,000 mg on day 1 every 28 days; continue for at least 3 cycles until best response or a maximum of 12 cycles (in combination with chlorambucil) (Ref).
Premedication: Premedicate with oral acetaminophen (1,000 mg) or equivalent, an oral or IV antihistamine (eg, diphenhydramine 50 mg or cetirizine 10 mg orally or equivalent), and an IV corticosteroid (prednisolone 50 mg or equivalent). Full dose corticosteroid is recommended for the first 2 infusions; in the absence of infusion reaction ≥ grade 3, may reduce or omit corticosteroid dose for subsequent infusions.
Chronic lymphocytic leukemia, relapsed: Arzerra: IV: Cycle 1 (cycle is 28 days): 300 mg on day 1, followed by 1,000 mg on day 8; Subsequent cycles: 1,000 mg on day 1 every 28 days; continue for a maximum of 6 cycles (in combination with fludarabine and cyclophosphamide) (Ref).
Premedication: Premedicate with oral acetaminophen (1,000 mg) or equivalent, an oral or IV antihistamine (eg, diphenhydramine 50 mg or cetirizine 10 mg orally or equivalent), and an IV corticosteroid (prednisolone 50 mg or equivalent). Full dose corticosteroid is recommended for the first 2 infusions; in the absence of infusion reaction ≥ grade 3, may reduce or omit corticosteroid dose for subsequent infusions.
Chronic lymphocytic leukemia, refractory: Arzerra: IV: Initial dose: 300 mg on day 1, followed 1 week later by 2,000 mg once weekly for 7 doses (doses 2 to 8), followed 4 weeks later by 2,000 mg once every 4 weeks for 4 doses (doses 9 to 12; for a total of 12 doses) (Ref).
Premedication: Premedicate with oral acetaminophen (1,000 mg) or equivalent, an oral or IV antihistamine (eg, diphenhydramine 50 mg or cetirizine 10 mg orally or equivalent), and an IV corticosteroid (prednisolone 100 mg or equivalent). Full dose corticosteroid is recommended for doses 1, 2, and 9; in the absence of infusion reaction ≥ grade 3, may reduce or omit corticosteroid dose for doses 3 to 8; may administer reduced corticosteroid dose (ranging from half to full dose) with doses 10 to 12 if ≥ grade 3 reaction did not occur with dose 9.
Chronic lymphocytic leukemia, extended treatment: Arzerra: IV: 300 mg on day 1, followed by 1,000 mg on day 8, followed by 1,000 mg 7 weeks later and then every 8 weeks for up to a maximum of 2 years (Ref).
Premedication: Premedicate with oral acetaminophen (1,000 mg) or equivalent, an oral or IV antihistamine (eg, diphenhydramine 50 mg or cetirizine 10 mg orally or equivalent), and an IV corticosteroid (prednisolone 50 mg or equivalent). Full dose corticosteroid is recommended for the first 2 infusions; in the absence of infusion reaction ≥ grade 3, may reduce or omit corticosteroid dose for subsequent infusions.
Multiple sclerosis, relapsing: Kesimpta:
Note: Administer all live or live-attenuated vaccines at least 4 weeks prior and non-live vaccines at least 2 weeks prior to initiation of therapy. Screen for hepatitis B prior to initiation; do not administer to patients with active hepatitis B confirmed by hepatitis B surface antigen (HBsAg) and anti-hepatitis B virus (HBV) tests. For patients with past HBV infections who are negative for HBsAg and positive for hepatitis B core antibody [HBcAb+] or are chronic carriers of HBV [HBsAg+], consult liver specialists before starting and during treatment. Obtain quantitative serum immunoglobulins prior to therapy initiation; for patients with low serum immunoglobulins, consult immunology specialists prior to initiation. In high-risk populations or in countries with high tuberculosis burden, screen for latent infections (eg, hepatitis, tuberculosis) prior to initiating therapy. For patients who screen positive for latent infections, consult infectious disease or other specialists (eg, liver specialists) regarding treatment options before initiating therapy (Ref).
SUBQ: Initial: 20 mg once weekly for 3 doses (weeks 0, 1, and 2); maintenance: 20 mg once monthly starting at week 4.
Missed dose: Administer as soon as possible without waiting until next scheduled dose; administer subsequent doses at the recommended intervals.
Waldenström macroglobulinemia, relapsed/refractory (off-label use):
Monotherapy: IV: 300 mg once during week 1, followed by 2,000 mg once weekly during weeks 2 to 5 of each treatment cycle. If stable disease or minor response occurred at 16 weeks following the first cycle (C1), patients could receive a redosing cycle (RC). Response was reassessed at 16 weeks following RC; if response occurred following C1 or RC and progressive disease subsequently developed within 36 months, cycle 2 (C2) could be administered. Refer to protocol for further information (Ref).
OFC regimen: IV: Cycle 1 (cycle is 28 days): 300 mg on day 1, followed by 1,000 mg on day 8. Subsequent cycles: 1,000 mg on day 1 every 28 days; continue for a total of 4 cycles (in combination with fludarabine and cyclophosphamide) (Ref).
Bendamustine/ofatumumab regimen: IV: Cycle 1 (cycle is 28 days): 300 mg on day −7 prior to cycle 1 only, followed by 1,000 mg on day 1. Subsequent cycles: 1,000 mg on day 1 every 28 days; continue for up to a total of 6 cycles (in combination with bendamustine) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
IV: Arzerra:
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's US labeling; however, there were no clinically relevant pharmacokinetic effects observed in patients with baseline CrCl ≥30 mL/minute.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
SUBQ: Kesimpta: There are no dosage adjustments provided in the manufacturer's US labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
IV: Arzerra:
Infusion reaction: Interrupt infusion for infusion reaction (any severity). If the reaction resolves or remains at ≤ grade 2, resume with the following modifications (based on the grade of the initial reaction):
Grade 1 or 2 infusion reaction: Resume at one-half of the previous rate; may increase (see Administration) based on patient tolerance.
Grade 3 or 4 infusion reaction: Resume infusion at 12 mL/hour; may increase (see Administration) based on patient tolerance.
If reaction severity does not resolve to ≤ grade 2 despite management: Consider permanent discontinuation
Anaphylactic reaction: Discontinue ofatumumab permanently.
Hepatitis B virus reactivation: Discontinue ofatumumab (and concomitant chemotherapy/immunosuppressants) if viral hepatitis develops and initiate appropriate antiviral therapy. The safety of resuming ofatumumab treatment following hepatitis B virus (HBV) reactivation is not known; discuss reinitiation of therapy in patients with resolved HBV reactivation with physicians experienced in HBV management.
Progressive multifocal leukoencephalopathy: Withhold ofatumumab immediately at the first sign/symptom suggestive of progressive multifocal leukoencephalopathy (PML) (symptoms may include altered mental status, motor deficits [hemiparesis or monoparesis], limb/gait ataxia, and/or vision disturbances) and perform a diagnostic evaluation.
SUBQ: Kesimpta:
Injection-related reaction: Manage with symptomatic treatment.
Progressive multifocal leukoencephalopathy: Withhold ofatumumab immediately at the first sign/symptom suggestive of PML (symptoms may include altered mental status, motor deficits [hemiparesis or monoparesis], limb/gait ataxia, and/or vision disturbances) and perform a diagnostic evaluation. Discontinue ofatumumab treatment if PML is confirmed.
Severe opportunistic or recurrent infections (with low immunoglobulins) or prolonged hypogammaglobulinemia requiring immunoglobulin treatment: Consider ofatumumab discontinuation.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Antineoplastic:
Dermatologic: Skin rash (14%)
Gastrointestinal: Diarrhea (18%), nausea (11%)
Hematologic & oncologic: Anemia (16%; grades 3/4: 5%), neutropenia (24%; ≥ grade 3: ≥22%; may be prolonged >2 weeks)
Infection: Infection (65% to 70%; includes bacterial, fungal, or viral), serious infection (20%)
Nervous system: Fatigue (15%)
Respiratory: Bronchitis (9% to 11%), cough (19%), dyspnea (14%), pneumonia (8% to 23%), upper respiratory tract infection (11% to 19%)
Miscellaneous: Fever (20%), infusion related reaction (46%; day 1 reactions: 25% to 44%; subsequent infusions: 2% to 29%)
Multiple sclerosis:
Infection: Infection (52%), serious infection (3%)
Local: Injection site reaction (systemic [chills, fatigue, fever, myalgia]: 21%; local: [erythema, pain, pruritus, swelling]: 11%)
Nervous system: Headache (13%)
Respiratory: Upper respiratory tract infection (39%)
1% to 10%:
Antineoplastic:
Cardiovascular: Hypertension (5%), hypotension (5%), peripheral edema (9%), tachycardia (5%)
Dermatologic: Hyperhidrosis (5%), urticaria (8%)
Hematologic & oncologic: Hypogammaglobulinemia (5%; grades 3/4: <1%)
Infection: Herpes zoster infection (5% to 6%), influenza (6%), sepsis (8%)
Nervous system: Chills (8%), headache (6%), insomnia (5% to 7%)
Neuromuscular & skeletal: Back pain (5% to 8%), muscle spasm (5%)
Respiratory: Nasopharyngitis (8%), sinusitis (5%)
Multiple sclerosis:
Genitourinary: Urinary tract infection (10%)
Hematologic & oncologic: Decreased serum immunoglobulins (immunoglobulin M: 6% to 8%)
Neuromuscular & skeletal: Back pain (8%)
<1%: Immunologic: Antibody development
Postmarketing:
Dermatologic: Stevens Johnson syndrome
Endocrine & metabolic: Porphyria cutanea tarda
Hematologic & oncologic: Tumor lysis syndrome
Hepatic: Hepatitis B (new-onset or reactivation)
Nervous system: Progressive multifocal leukoencephalopathy
IV (Arzerra): There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to ofatumumab or any component of the formulation; presence or history of progressive multifocal leukoencephalopathy.
SUBQ (Kesimpta): Active hepatitis B virus infection.
Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to ofatumumab or any component of the formulation; severe active infection; presence or history of progressive multifocal leukoencephalopathy; patients in a severely immunocompromised state; patients with active malignancies.
Concerns related to adverse effects:
• Hematologic toxicity (Arzerra): Severe and prolonged (≥1 week) cytopenias (neutropenia, thrombocytopenia, and anemia) may occur. Grade 3 or 4 late-onset neutropenia (onset ≥42 days after last treatment dose) and/or prolonged neutropenia (not resolved 24 to 42 days after last dose) have been reported. Pancytopenia, agranulocytosis, and fatal neutropenic sepsis have occurred when used in combination with chlorambucil.
• Hepatitis B virus reactivation: Hepatitis B virus (HBV) reactivation may occur in patients receiving CD20-directed antibody treatment, including ofatumumab for chronic lymphocytic leukemia (CLL); may result in fulminant hepatitis, hepatic failure, and death. Fatal cases of HBV have also occurred in patients not previously infected with HBV. HBV reactivation has not been reported in multiple sclerosis (MS) clinical studies; ofatumumab is used at higher doses and for shorter duration of therapy for CLL. HBV reactivation has been reported up to 12 months after CLL therapy discontinuation. Reactivation has occurred in patients who are HBsAg positive as well as in those who are HBsAg negative but are anti-HBc positive; HBV reactivation has also been observed in patients who had previously resolved HBV infection. For patients with evidence of prior HBV infection (eg, HBsAg positive [regardless of antibody status] or HBsAg negative but anti-HBc positive), consult with appropriate clinicians (eg, liver disease experts) regarding monitoring and consideration of antiviral therapy before and/or during ofatumumab treatment.
• Immunoglobulin reduction (Kesimpta): Decrease in immunoglobulin levels may occur with ofatumumab. Consult immunology experts prior to initiation for patients with low serum immunoglobulins.
• Infection: Bacterial, fungal, and new or reactivated viral infections may occur during and/or following therapy. In patients with MS, ofatumumab is associated with an increased risk for upper respiratory tract and urinary tract infections. In high-risk populations or in countries with high tuberculosis burden, screen for latent infections (eg, hepatitis, tuberculosis) prior to initiating therapy. For patients who screen positive for latent infections, consult infectious disease or other specialists (eg, liver specialists) regarding treatment options before initiating therapy (AAN [Farez 2019]). Delay administration in patients with active infections until the infection has resolved. When initiating ofatumumab before or after other immunosuppressive therapy, increased immunosuppressive effects may occur.
• Infusion reaction (Arzerra): May cause serious infusion reactions (some fatal); reactions may include bronchospasm, dyspnea, laryngeal edema, pulmonary edema, flushing, hypertension, hypotension, syncope, cardiac ischemia/infarction, acute coronary syndrome, arrhythmia, bradycardia, back pain, abdominal pain, fever, rash, urticaria, angioedema, cytokine-release syndrome, and/or anaphylactoid/anaphylactic reactions. Infusion reactions occur more frequently with the first 2 infusions and may occur despite premedication.
• Injection-related reactions (Kesimpta): Systemic and local injection reactions, including fever, headache, myalgia, chills, fatigue, erythema, swelling, itching, and pain, may occur with SUBQ ofatumumab. Premedication with corticosteroids, antihistamines, or acetaminophen is of limited benefit. The first injection should be performed under the guidance of an appropriately trained health care professional. Incidence of injection-related reactions may be higher with the first injection, most commonly within 24 hours, and decrease with subsequent injections.
• Progressive multifocal leukoencephalopathy: Progressive multifocal leukoencephalopathy (PML) resulting in death may occur with CD20-directed antibody treatment for CLL, including ofatumumab. No reports of PML have occurred in MS clinical studies; ofatumumab is used at higher doses and for shorter duration of therapy for CLL. PML findings may be detected by MRI before clinical signs or symptoms.
• Tumor lysis syndrome (Arzerra): Tumor lysis syndrome (TLS) has occurred in patients receiving ofatumumab; patients with a high tumor burden and/or high circulating lymphocyte counts (>25,000/mm3) are at increased risk for TLS.
Concurrent drug therapy issues:
• Immunizations: Live vaccines should not be administered to patients who have recently received ofatumumab; there are no data concerning secondary transmission. The ability to generate an immune response to any vaccine following treatment is unknown. When using for the treatment of MS, administer live and live-attenuated vaccines at least 4 weeks prior to initiation of therapy; administer inactivated vaccines at least 2 weeks prior to initiation of therapy. Live and live-attenuated vaccination is not recommended during treatment and after discontinuation until repletion of B-cells; consider using live-attenuated vaccines for patients with MS only if risk of infection is high and killed vaccines are unavailable (AAN [Farez 2019]).
Special populations:
• Elderly (Arzerra): Patients ≥65 years of age experienced a higher incidence of adverse reactions (compared with patients <65 years of age).
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Concentrate, Intravenous [preservative free]:
Arzerra: 100 mg/5 mL (5 mL); 1000 mg/50 mL (50 mL) [contains edetate disodium, mouse (murine) and/or hamster protein, polysorbate 80]
Solution Auto-injector, Subcutaneous [preservative free]:
Kesimpta: 20 mg/0.4 mL (0.4 mL) [contains disodium edta, polysorbate 80]
No
Concentrate (Arzerra Intravenous)
100 mg/5 mL (per mL): $0.00
1000 mg/50 mL (per mL): $0.00
Solution Auto-injector (Kesimpta Subcutaneous)
20 mg/0.4 mL (per 0.4 mL): $10,482.70
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Auto-injector, Subcutaneous:
Kesimpta: 20 mg/0.4 mL (0.4 mL) [contains disodium edta, polysorbate 80]
Arzerra is no longer commercially available, but may be obtained via the Arzerra Oncology Access Program. Further information is available from Novartis (1-800-282-7630) or https://www.us.arzerra.com/.
IV: Arzerra: Do not administer IV push, IV bolus, or as a subcutaneous injection. Premedicate with acetaminophen, an antihistamine, and a corticosteroid 30 to 120 minutes prior to administration (see Dosing). Infuse in an environment equipped to monitor for and manage infusion reactions. Administer with infusion pump and administration set. Do not exceed infusion rates below. Do not mix with or infuse with other medications. Flush line before and after infusion with NS. Begin infusion within 12 hours of preparation. Interrupt infusion for any severity of infusion reaction; if the reaction resolves or remains at ≤ grade 2, may resume infusion (see Dosage Adjustment for Toxicity).
Previously untreated chronic lymphocytic leukemia (CLL), relapsed CLL, and extended treatment of CLL:
Initial 300 mg dose: Initiate infusion at 12 mL/hour for 30 minutes, if tolerated (no infusion reaction) increase to 25 mL/hour for 30 minutes, if tolerated, increase to 50 mL/hour for 30 minutes, if tolerated, increase to 100 mL/hour for 30 minutes, if tolerated, increase to 200 mL/hour for 30 minutes, if tolerated increase to 300 mL/hour for 30 minutes, if tolerated, increase to 400 mL/hour for remainder of infusion. Median duration of infusion: 4.8 to 5.2 hours.
Subsequent 1,000 mg infusions (if no reaction to previous infusion): Initiate infusion at 25 mL/hour for 30 minutes, if tolerated (no infusion reaction) increase to 50 mL/hour for 30 minutes, if tolerated, increase to 100 mL/hour for 30 minutes, if tolerated, increase to 200 mL/hour for 30 minutes, if tolerated, increase to 400 mL/hour for remainder of infusion. Median duration of infusion: 4.2 to 4.4 hours.
Refractory CLL:
Doses 1 and 2: Initiate infusion at 12 mL/hour for 30 minutes, if tolerated (no infusion reaction) increase to 25 mL/hour for 30 minutes, if tolerated, increase to 50 mL/hour for 30 minutes, if tolerated, increase to 100 mL/hour for 30 minutes, if tolerated, increase to 200 mL/hour for remainder of infusion. Median duration of infusion: 6.8 hours.
Doses 3 to 12: Initiate infusion at 25 mL/hour for 30 minutes, if tolerated (no infusion reaction) increase to 50 mL/hour for 30 minutes, if tolerated, increase to 100 mL/hour for 30 minutes, if tolerated, increase to 200 mL/hour for 30 minutes, if tolerated, increase to 400 mL/hour for remainder of infusion. Median duration of infusion: 4.2 to 4.4 hours.
SUBQ: Kesimpta: Administer only by SUBQ injection in the abdomen, thigh, or outer upper arm; avoid moles, scars, stretch marks, or areas where the skin is tender, bruised, red, scaly, or hard. The first injection should be performed under the guidance of a health care professional. Sensoready pens and syringes are for one-time use only; discard after use.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Kesimpta: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125326s075lbl.pdf#page=13
Chronic lymphocytic leukemia, previously untreated: Arzerra: Treatment of previously untreated chronic lymphocytic leukemia (CLL) (in combination with chlorambucil) when fludarabine-based therapy is considered inappropriate.
Chronic lymphocytic leukemia, relapsed : Arzerra: Treatment of relapsed CLL (in combination with fludarabine and cyclophosphamide).
Chronic lymphocytic leukemia, refractory: Arzerra: Treatment of CLL refractory to fludarabine and alemtuzumab.
Chronic lymphocytic leukemia, extended treatment: Arzerra: Extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL.
Multiple sclerosis, relapsing: Kesimpta: Treatment of relapsing forms of multiple sclerosis (in adults), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.
Waldenström macroglobulinemia, relapsed/refractory
Ofatumumab may be confused with obiltoxaximab, obinutuzumab, ocrelizumab, olaratumab, omalizumab, rituximab
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Antithymocyte Globulin (Equine): Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of anti-CD20 B-cell depleting therapy is reduced. Anti-CD20 B-Cell Depleting Therapies may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chikungunya Vaccine (Live): Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
Corticosteroids (Systemic): May enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
COVID-19 Vaccines: Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of COVID-19 Vaccines. Management: Administer COVID-19 vaccine 2 to 4 weeks prior to the next scheduled dose of anti-CD20 therapy, if used chronically for the treatment of autoimmune disease. Revaccinate 6 months after completion of anti-CD20 therapy if used over a limited period. Risk D: Consider therapy modification
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Immunosuppressants (Cytotoxic Chemotherapy): May enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Immunosuppressants (Miscellaneous Oncologic Agents): May enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Immunosuppressants (Therapeutic Immunosuppressant Agents): May enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines 2 weeks prior to starting anti-CD20 B-cell depleting therapies. Vaccination of patients treated with these agents in the past 6 months is not recommended. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Methotrexate: May enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Mumps- Rubella- or Varicella-Containing Live Vaccines: Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Poliovirus Vaccine (Live/Trivalent/Oral): Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation or 6 months after anti-CD20 B-cell depleting therapies. If vaccinated prior to B cell recovery, consider assessing immune response to vaccination. Risk D: Consider therapy modification
Vaccines (Live): Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Anti-CD20 B-Cell Depleting Therapies may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Patients who can become pregnant should use effective contraception during therapy and for 6 months after the last dose of ofatumumab.
In general, disease-modifying therapies for multiple sclerosis (MS) are stopped prior to a planned pregnancy except in patients at high risk of MS activity (AAN [Rae-Grant 2018]). Consider use of agents other than ofatumumab for patients at high risk of disease reactivation who are planning to become pregnant. Delaying pregnancy is recommended for patients with persistent high disease activity; when disease-modifying therapy is needed in these patients, other agents are preferred (ECTRIMS/EAN [Montalban 2018]).
Ofatumumab is a humanized monoclonal antibody (IgG1). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).
Based on data from animal reproduction studies and human data from other anti-CD20 antibodies, transient peripheral B-cell depletion and lymphocytopenia may occur in newborns exposed to ofatumumab in utero.
Outcome data following maternal use of ofatumumab during pregnancy are limited (Dobson 2023; Hellwig 2022, Kranjnc 2022; Quattrocchi 2016). In general, disease-modifying therapies for multiple sclerosis (MS) are not initiated during pregnancy, except in patients at high risk of MS activity (AAN [Rae-Grant 2018]). When disease-modifying therapy is needed in these patients, other agents are preferred (ECTRIMS/EAN [Montalban 2018]).
Data collection to monitor pregnancy and infant outcomes following exposure to ofatumumab is ongoing. Health care providers are encouraged to enroll patients exposed to ofatumumab during pregnancy in the MotherToBaby Pregnancy Study in Multiple Sclerosis (1-877-311-8972); patients may also enroll themselves.
It is not known if ofatumumab is present in human milk.
Ofatumumab is a humanized monoclonal antibody (IgG1). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Anderson 2021). Outcome data following the use of ofatumumab in lactating patients is limited (Schwake 2022).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of exposure to the infant and the benefits of treatment to the mother.
IV:
CBC with differential (at regular intervals during and after therapy; more frequently if grades 3 or 4 cytopenias develop), renal function, electrolytes.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Monitor for signs of active hepatitis B infection (during and for up to 12 months after therapy completion). Monitor fluid status. Monitor for signs/symptoms of hepatitis, infusion reaction, infection intestinal obstruction (eg, abdominal pain, repeated vomiting), and progressive multifocal leukoencephalopathy (PML) (focal neurologic deficits, which may present as hemiparesis, visual field deficits, cognitive impairment, aphasia, ataxia, and/or cranial nerve deficits).
SUBQ: Monitor quantitative serum immunoglobulins (at baseline, throughout treatment as clinically necessary, especially in patients with opportunistic or recurrent infections, after discontinuation of therapy until B-cell repletion); HBsAg, hepatitis B core antibody (HBcAb), and other hepatitis B markers as per local guidelines (baseline and as clinically necessary); latent infection screening (eg, hepatitis, tuberculosis) in high-risk populations or in countries with high tuberculosis burden (baseline). Monitor for signs/symptoms of PML (eg, altered mental status, motor deficits [hemiparesis or monoparesis], limb/gait ataxia, and/or vision disturbances); monitor MRI (as clinically indicated).
Ofatumumab is a monoclonal antibody which binds specifically the extracellular (large and small) loops of the CD20 molecule (which is expressed on normal B lymphocytes and in B-cell CLL) resulting in potent complement-dependent cell lysis and antibody-dependent cell-mediated toxicity in cells that overexpress CD20.
Distribution: Vdss (following repeated administrations): IV: 6.1 L; SUBQ: 5.4 L.
Metabolism: Expected pathway is degradation to small peptides and amino acids by proteolytic enzymes.
Half-life elimination (following repeated administrations): IV: 17.6 days; SUBQ: ~16 days. Higher baseline B-cell counts at the start of therapy result in a greater component of target-mediated elimination and a shorter ofatumumab half-life at the start of therapy.
Excretion: Eliminated via both target-independent and target-mediated B-cell binding routes; not likely to undergo renal excretion.
Clearance: IV: 9.3 mL/hour; SUBQ (after B-cell depletion): 0.34 L/day.
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